In recent years there have been a number of advances in SPECT imaging including improvements in reconstruction and compensation methods, and imaging systems. However, much of this work has been targeted at improvement of diagnostic procedures. The collection of quantitative imaging information is a critical step in dosimetry and treatment planning for targeted radionuclide therapy (TRT). Errors in the quantitative imaging methods can result in reduced efficacy or increased incidence of adverse side effects. The most commonly used quantitation methodology for TRT dosimetry is conjugate-view planar imaging, a method pioneered more than 20 years ago. The goal of this project is to develop, optimize, and evaluate, practical and clinically implementable quantitative imaging methods for use in estimating in vivo the cumulated activity (i.e., the number of radioactive decays that occur in a region or organ integrated over time). The methods will be Dased on combinations of planar and one or more SPECT scans performed on a SPECT/CT system and processed using quantitative SPECT reconstruction and planar processing techniques. Specifically, SPECT reconstruction algorithms for ln-111 and 1-131 photon emissions that account for scatter, attenuation, partial volume effects, and collimator penetration and scatter will be developed. Planar imaging methods that incorporate lateral as well as AP imaging acquisition and organ overlap correction based on SPECT scans will be examined to improve organ and tumor delineation and radioactivity quantitation. Monte Carlo simulations, physical phantoms, and patient data will be used to optimize and validate the methodologies. A population of mathematical phantoms, based on the results of patient studies, will be developed and used to model various anatomies and pharmacokinetics. The imaging parameters and acquisition techniques will be evaluated in terms of their influence on the estimation of dosimetric parameters. Quantitative imaging is a critical input to dosimetry calculations that are essential to TRT treatment planning. The work described in this proposal will develop and validate methodologies for improving quantitation in a practical and clinically implementable manner. If successful, this project will allow the development of more accurate treatment plans with the potential for greater therapeutic effect and fewer adverse reactions. It will also provide valuable methodological improvements for clinical studies trying to understand TRT dose-response relationships.